VitD3 Supplementation in Patients With Multiple Myeloma

Официальное название

EVALUATION OF CHOLECALCIFEROL (VitD3) MAINTENANCE SUPPLEMENTATION IN PATIENTS WITH MULTIPLE MYELOMA (MM) UNDERGOING TRANSPLANTATION AND IN COMBINATION WITH LENALIDOMIDE MAINTENANCE

Обзор

The goal of this clinical trial is to evaluate post-transplant immune reconstitution and lymphocyte recovery as well as the 3-year progression-free survival of patients with multiple myeloma in two treatment arms. One arm will receive Maintenance Vitamin D and the other arm will receive no maintenance Vitamin D prior to ASCT. Post ASCT arm 1 will have lenalidomide and maintenance VitD, and arm 2 will receive lenalidomide and no maintenance VitD. This clinical trial will also evaluate the overall response rate and survival for both treatment arms.

Подробное описание

Management of multiple myeloma (MM) has changed significantly over the past 10 years. The use of three drug induction therapy followed by autologous stem cell transplantation (ASCT) has become standard of care for transplant eligible patients with MM since randomized trials showed improved progression-free survival (PFS) and overall survival (OS) with three drugs, albeit in the non-transplant setting.

Evidence suggests Vitamin D deficiency is correlated with poorer outcomes in this population; however, it is unknown if intensified Vitamin D supplementation improves outcomes. This clinical trial aims to address this question and will postulate the impact of Vitamin D on immunoregulatory functions and the hematopoietic niche microenvironment.

Вмешательства

• Препарат Lenalidomide
  For first three cycles, taken orally once daily for 28 days at 10mg/day dose. After cycle 4, taken orally once daily at 15 mg/day dose
• Препарат Maintenance Vitamin D
  After replacement of vitamin D deficiency with weekly cholecalcefirol 50,000 units untill levels are \> 30, will start maintenance therapy with Monthly replacement with 50,000 IU
• Препарат No maintenance Vitamin D
  After replacement of vitamin D deficiency with weekly cholecalcefirol 50,000 units untill levels are \> 30, stop replacement and continue monitoring levels

Первичные конечные точки

• To describe the lymphocyte subset analysis for the two treatment arms at 120 days post autologous stem cell transplant [120 days] [Срок оценки: 120 days]

Вторичные конечные точки (8)

• 3 year progression free survival [Срок оценки: 3 years]
• Overall Response Rate post 120 days of ASCT [Срок оценки: 120 Days]
• Overall Response Rate after transplantation [Срок оценки: Two Years]
• 3 Year Overall Survival after transplantation [Срок оценки: Three Years]
• Minimal Residual Disease status [Срок оценки: Randomization; 120 days after transplantation; two years after transplantation.]
• Vitamin D levels [Срок оценки: Before autologous stem cell transplant; 120 days after transplantation; three years post-transplantation]
• Adverse Event Reporting [Срок оценки: Three years]
• Neutrophil and Platelet Engraftment and Transfusion Independence [Срок оценки: After transplantation, an average of 30 days]

Критерии участия

Критерии включения

• Patients must be ≥ 18 years of age at time of registration to Step 1.
• Patients must have history and physical exam within 28 days prior to registration.
• Patients must have Zubrod/ECOG Performance Status ≤ 2.
• Patients must have had a confirmed diagnosis of symptomatic MM (See Section 4.1) with measurable disease at the time of myeloma diagnosis that required systemic induction therapy prior to ASCT. Measurable disease is defined as measurable M protein in the serum (≥ 0.5g/dL) or urine (≥ 200 mg/24h) or serum free light chain assay (defined as ≥ 10 mg/dL \[≥ 100 mg/L\] on involved light chain) at the time of diagnosis. Patients with smoldering myeloma are not eligible until they have progressed to symptomatic myeloma.
• Patients must be willing and able to take DVT prophylaxis (aspirin, low molecular weight heparin, warfarin, or equivalent oral anticoagulation) and comply with lenalidomide REMS program requirements.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration. FCBP must agree to have a second pregnancy test within 24 hours prior to starting lenalidomide. Further, FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide. FCBP must also agree to ongoing pregnancy testing and must agree to not become pregnant for at least 3 months after the last dose of study treatment. A FCBP is a female who: 1) has achieved menarche (first menstrual cycle) at some point, 2) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months).Men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy, during the study treatment and for 3 months after the last dose of study treatment.
• Patients must have evidence of adequate renal function, as defined by (1) creatinine clearance (CrCl) ≥ 10 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula. Values must be obtained within 28 days prior to registration. Estimated creatinine clearance = (140 - age) x wt (kg) x 0.85 (if female) 72 x creatinine (mg/dl)
• Patients must have adequate hepatic function defined by the following within 28 days prior to registration: Total bilirubin ≤ 1.5 x IULN (institutional upper limit of the norm) and AST and ALT ≤ 3.0 x IULN
• Patients must be acceptable for transplant per institutional guidelines:
• Patient's with human immunodeficiency virus (HIV) are eligible providing they are on effective antiretroviral therapy and have undetectable viral load at their most previous viral load test and within 6 months prior to registration.
• Patients must be able to take and swallow oral medication (capsules) whole.
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Критерии исключения

• Any organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction.
• Progressive disease at any time prior to registration.
• Intolerance to the starting dose of lenalidomide (10 mg).
• Prior allograft, prior organ transplant requiring immunosuppressive therapy, or have already received a previous autologous transplantation (e.g., requiring second ASCT at time of screening).
• Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
• Received any investigational agents within 14 days prior to registration.
• Seropositive for Hepatitis B
• Seropositive for Hepatitis C
• Hypercalcemia (serum calcium level > 10.3 mg/dL) (institutional upper limit of the norm) at time of study entry.
• Patients refractory to lenalidomide.
• Patients that have received any investigational agents within 14 days prior to registration.
• Any known impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). h known allergies to any of the study drugs.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Georgia Cancer Center at Augusta University — Augusta

Идентификаторы

NCT: NCT05846880 · GCC-22-044

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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